PMID: 

Int Immunopharmacol. 2020 Feb ;79:106070. Epub 2020 Jan 6. PMID: 31918062

Abstract Title: 

Effects of luteolin on treatment of psoriasis by repressing HSP90.

Abstract: 

AIMS: This study was conducted to further clarify the efficacy and potential of luteolin in treating psoriasis and to explore its inner mechanisms.METHODS: A pharmacology network displayed the construction of a drug disease target prediction method. The prediction technique was validated via cell experiments in vitro and animal experiments in vivo, respectively. The effects of IFN-γ and luteolin were detected in HaCaT cells. The secretion of exosome and expression of mRNA and protein were detected to explain the relationship between luteolin's regulation of HSP90 (HSP90α and HSP90β) activity in vitro. An in vivo psoriasis mouse model was established to further explore theefficacy of luteolin. Morphological and histological changes in skin lesions were observed, and the CD63, calnexin, Hsp90α, and Hsp90β protein expression was analyzed. Peripheral blood mononuclear cells (PBMCs) were separated and detected via flow pattern analysis to determine how luteolin effectsthe immune cells in a psoriasis model.RESULTS: Luteolin as a candidate compound is predicted to have a molecular-target correspondence with HSP90 according to a pharmacology network analysis. Cell experiments indicated that the pathogenesis of psoriasis was significantly related to the increase in IFN-γ, which promoted the transcriptional expression and exosome secretion of HSP90 in HaCaT cells; conversely, luteolin inhibited those and alleviated the promotion of IFN-γ. The effect of luteolin on HSP90 was slightly weaker than that of INF-γ. Animal experiments indicated that the efficacy of luteolin was similar to that of 17-AAG, which both alleviated skin tissue lesions and symptoms, improved the expression of Hsp90 mRNA and protein in skin tissue, and promoted exosome secretion of Hsp90 in plasma. For immune cells in mice with psoriasis, luteolin reduced the proportion of Th1/Th2 and Th17/Treg and inhibited the increase in Th1 and Th17 in the peripheral blood.CONCLUSION: Luteolin can relieve the lesions and symptoms of psoriasis through reversing the effects of IFN-γ, inhibiting the expression and exosome secretion of HSP90, and regulating the proportion of immunocytes. Therefore, this study provides the possible mechanisms and potential utilization of luteolin as a novel treatment for psoriasis.

read more

PMID: 

Br J Pharmacol. 2020 Jan 24. Epub 2020 Jan 24. PMID: 31976547

Abstract Title: 

Luteolin prevents irinotecan-induced intestinal mucositis in mice through antioxidant and anti-inflammatory properties.

Abstract: 

BACKGROUND AND PURPOSE: Intestinal mucositis refers to mucosal damage caused by cancer treatment and irinotecan is one of the agents most associated with this condition. Focusing on the development of alternatives to prevent this important adverse effect, we evaluated the activity of the flavonoid luteolin, which has never been tested for this purpose despite its biological potential.EXPERIMENTAL APPROACH: The effects of luteolin were examined on irinotecan-induced intestinal mucositis in mice. Clinical signs were evaluated. Moreover, histological, oxidative and inflammatory parameters were analyzed, as well as the possible interference of luteolin in the antitumor activity of irinotecan.KEY RESULTS: Luteolin at 30 mg/kg (p.o. or i.p), prevents irinotecan-induced intestinal damage by reducing weight loss and diarrhea score and attenuating the shortening of the duodenum and colon. The histological analysis confirmed that luteolin (30 mg/kg, p.o.) prevented villous shortening, vacuolization, and apoptosis of cells and preserved mucin production in the duodenum and colon. Moreover, luteolin treatment mitigated irinotecan-induced oxidative stress (i.e. by reducing the levels of ROS and LOOH, and augmenting endogenous antioxidants) and inflammation (i.e. through the decrease of MPO enzyme activity, TNF, IL-1β, and IL-6 levels; and increasing IL-4 and IL-10). Besides, the disruption of the tight junctions ZO-1 and occludin were also prevented by luteolin treatment. Importantly, luteolin did not interfere with the antitumor activity of irinotecan.CONCLUSION AND IMPLICATIONS: Luteolin prevents intestinal mucositis induced by irinotecan and therefore could be a potential adjunct in antitumor therapy to control this adverse effect, increasing treatment adherence and consequently the chances of cancer remission.

read more

PMID: 

Cancer Sci. 2020 Jan 29. Epub 2020 Jan 29. PMID: 31994822

Abstract Title: 

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin (mTOR) pathway.

Abstract: 

Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cell-cycle arrest, p21 up-regulation and down-regulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend in decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Further, the major findings in the metabolism of luteolin suggests both plasma and urine luteolin-3'-O -glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentrations. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by up-regulating p21 and inhibiting mTOR signaling.

read more

PMID: 

Anticancer Res. 2020 Feb ;40(2):723-731. PMID: 32014914

Abstract Title: 

Luteolin-regulated MicroRNA-301-3p Targets Caspase-8 and Modulates TRAIL Sensitivity in PANC-1 Cells.

Abstract: 

BACKGROUND/AIM: MicroRNAs (miRNAs) play regulatory roles in pancreatic ductal adenocarcinoma (PDAC). However, it is still required to identify the function of miRNA-301-3p in pancreatic cancer cells.MATERIALS AND METHODS: Effects of luteolin on cell growth, TRAIL cytotoxicity, and miR-301-3p levels were evaluated. The role of miRNA-301-3p in regulating cell proliferation, target gene expression, and TRAIL cytotoxicity were studied.RESULTS: The levels of miR-301-3p were down-regulated in PANC-1 cells exposed to luteolin, which inhibits the growth of PANC-1 cells and sensitizes cells to TRAIL. The knockdown of miR-301-3p attenuates cell proliferation and enhances TRAIL cytotoxicity. In addition, caspase-8 was directly targeted by miR-301-3p.CONCLUSION: Our findings unveil a critical biological function of miR-301-3p in regulating cell proliferation and elevating an antiproliferative effect of TRAIL on cancer cells. Our observation of miR-301-3p/caspase-8 relationship can also serve to clarify the role of miR-301-3p in other cancer types and related diseases.

read more

PMID: 

Oxid Med Cell Longev. 2019 ;2019:6493081. Epub 2019 Dec 12. PMID: 31915512

Abstract Title: 

Coenzyme Q10 Regulation of Apoptosis and Oxidative Stress in HOInduced BMSC Death by Modulating the Nrf-2/NQO-1 Signaling Pathway and Its Application in a Model of Spinal Cord Injury.

Abstract: 

Spinal cord injury (SCI) has always been considered to be a devastating problem that results in catastrophic dysfunction, high disability rate, low mortality rate, and huge cost for the patient. Stem cell-based therapy, especially using bone marrow mesenchymal stem cells (BMSCs), is a promising strategy for the treatment of SCI. However, SCI results in low rates of cell survival and a poor microenvironment, which limits the therapeutic efficiency of BMSC transplantation. Coenzyme Q10 (CoQ10) is known as a powerful antioxidant, which inhibits lipid peroxidation and scavenges free radicals, and its combined effect with BMSC transplantation has been shown to have a powerful impact on protecting the vitality of cells, as well as antioxidant and antiapoptotic compounds in SCI. Therefore, we aimed to evaluate whether CoQ10 could decrease oxidative stress against the apoptosis of BMSCsand explored its molecular mechanisms. Furthermore, we investigated the protective effect of CoQ10 combined with BMSCs transplanted into a SCI model to verify its ability. Our results demonstrate that CoQ10 treatment significantly decreases the expression of the proapoptotic proteins Bax and Caspase-3, as shown through TUNEL-positive staining and the products of oxidative stress (ROS), while increasing the expression of the antiapoptotic protein Bcl-2 and the products of antioxidation, such as(GSH), against apoptosis and oxidative stress, in a HO-induced model. We also identified consistent results from the CoQ10 treatment of BMSCs transplanted into SCI rats. Moreover, the Nrf-2 signaling pathway was also investigated in order to detail its molecular mechanism, and the results show that it plays an important role, bothand. Thus, CoQ10 exerts an antiapoptotic and antioxidant effect, as well as improves the microenvironmentand. It may also protect BMSCs from oxidative stress and enhance their therapeutic efficiency when transplanted for SCI treatment.

read more

PMID: 

Cell Biochem Funct. 2020 Jan 27. Epub 2020 Jan 27. PMID: 31989689

Abstract Title: 

Coenzyme Q10 attenuates rat hepatocarcinogenesis via the reduction of CD59 expression and phospholipase D activity.

Abstract: 

The current study aimed to test the profile of serum lipids, phospholipase D (PLD) activity, and CD59 expression pattern in rat hepatocellular carcinoma (HCC) after therapeutic treatment with Coenzyme Q10 (CoQ10). Three rat groups were allocated as normal control, untreated HCC, and treated HCC (HCC + CoQ10). The levels of serum α-fetoprotein (AFP) and tumour necrosis factor (TNF)-α were assessed using enzyme-linked immunosorbent assay (ELISA), while proliferating cell nuclear antigen (PCNA) was detected using immunohistochemistry (IHC). Serum lipids, classical (CH50), and alternative (APH50) pathways of complement activation, the liver cell HMG-CoA reductase (HMGCR), and PLD activities were assayed colorimetrically. The protein expression of CD59, scavenger receptor class B type 1 (SRB1), B cell lymphoma-2 (Bcl2), and cleaved Caspase-3 (Casp-3) were detected using western blotting, while the level of serum CD59 (sCD59) was assessed using dot-blot. CoQ10 reduced the cell proliferation, histological alterations, and the levels of AFP and TNF-α but increased lipids, CH50, and sCD59 in serum. In the liver cell, CoQ10 decreased and increased PLD and HMGCR enzyme activities, respectively. In addition, reduction of liver CD59, Bcl2, and SRB1 vs increased cleaved Casp-3 expressions was observed. Statistical correlation indicated an inverse relationship between CH50 and each of CD59 expression and PLD activity after treatment with CoQ10. In conclusion, CoQ10 could protect against rat HCC through increased lipids and the reduction of CD59 expression and PLD activity. SIGNIFICANCE OF THE STUDY: To our knowledge, this study is the first to describe the attenuating effect of antitumour natural product like Coenzyme Q10 (CoQ10) via the reduction of CD59 expression and phospholipase D (PLD) activity. This illustrates the important role of CD59 and PLD in relation to lipids in cancer prevention.

read more

PMID: 

World J Mens Health. 2020 Jan 20. Epub 2020 Jan 20. PMID: 32009311

Abstract Title: 

Coenzyme Q10 Improves Sperm Parameters, Oxidative Stress Markers and Sperm DNA Fragmentation in Infertile Patients with Idiopathic Oligoasthenozoospermia.

Abstract: 

PURPOSE: Oxidative stress and sperm DNA fragmentation (SDF) are potential contributing factors for idiopathic male infertility. Coenzyme Q10 (CoQ10) have been reported to be effective in the treatment of idiopathic male infertility, in general, owing to its antioxidant properties. Thus, the present study intends to investigate the effects of CoQ10 therapy on semen parameters, oxidative stress markers and SDF in infertile men, specifically with idiopathic oligoasthenozoospermia (OA).MATERIALS AND METHODS: In this case-control study, sixty-five infertile patients with idiopathic OA and forty fertile men (control) were included. All participants underwent semen analysis based on the World Health Organization guidelines (5th edition, 2010). Patients received CoQ10 at the dose of 200 mg/d orally for three months. Seminal plasma CoQ10, total antioxidant capacity (TAC), total reactive oxygen species (ROS), glutathione peroxidase (GPx), and SDF levels were measured in controls (baseline) and infertile patients pre- and post-CoQ10 treatment.RESULTS: CoQ10 treatment for three months significantly improved sperm concentration (p

read more

PMID: 

Cell Stress Chaperones. 2020 Jan 18. Epub 2020 Jan 18. PMID: 31953635

Abstract Title: 

Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway.

Abstract: 

Vitiligo is a chronic, autoimmune destruction of melanocytes, resulting in progressively expanding depigmented skin patches. Severity of the disorder, which affects approximately 1% of humans, may be mitigated using topical corticosteroids combined with phototherapy; along with other clinical strategies; however, no definitive cures are currently available. Here, the capacity of apigenin, a plant-derived aglycone, to inhibit oxidative stress-mediated melanocyte depletion in vitro using a PIG3V vitiligo perilesional melanocyte cell model is evaluated. PIG3V cells, treated with selected doses of apigenin, were challenged with HO, then assessed for viability and the oxidative stress-related parameters: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) by enzyme-linked immunoabsorbent assay (ELISA). Additionally, expression of nuclear factor erythroid 2p45 (NF-E2)-related factor 2 (Nrf2) and downstream targets was detected using Western blotting. Outcomes demonstrated that compared with negative control cultures, apigenin-treated cells exhibited enhanced viability. Likewise, apigenin enhanced expression of the cellular anti-oxidants SOD, CAT, and GSH-Px, but inhibited production of MDA, an oxidative stress biomarker. Interestingly, the expression and nuclear localization of the Nrf2 transcription factor, an important regulator oxidative stress and its downstream target genes, was significantly increased by apigenin treatment. Apigenin influence on Nrf2 was further validated by experiments demonstrating that Nrf2 knockdown cells failed to exhibit significant apigenin-mediated effects on cell viability and oxidative stress. Apigenin's non-toxicity and ability to affect multiple oxidative stress-related parameters through its effects on Nrf2 signaling in melanocytes suggests that it may prove to be a valuable therapeutic tool in long-term management of vitiligo.

read more

PMID: 

J Dermatolog Treat. 2020 Feb 5:1-8. Epub 2020 Feb 5. PMID: 32022625

Abstract Title: 

Anthocyanins rich pomegranate cream as a topical formulation with anti-aging activity.

Abstract: 

Anthocyanins are antioxidant compounds constitute the primary dyes of the pomegranate arils. Anthocyanins could protect the aged skin induced by oxidant exposure as a major role in aging processing and skin degeneration.The study aimed to evaluate the anti-aging activity of anthocyanins rich pomegranate () after formulated into a topical cream. Also, its effect on human dermal fibroblast function and epidermal keratinocyte were evaluated.Anthocyanins were extracted from fresh pomegranate arils using acidified methanol and were purified by Sephadex LH-20 gel-column chromatography. Further, the fusion method was used to prepare cold cream containing pomegranate anthocyanins. The formulated cream was evaluated for their compatibility study, irritation, homogeneity, drug content, drug release, and stability tests. Furthermore, permeation study through abdominal rabbits, as well as Human application was performed.Compatibility study showed the absence of any interaction between anthocyanins and the used polymers. The formulated cream was nonirritant, homogenous and potentially reduced skin aging when applied to Human volunteers' skin. Furthermore, the skin permeation displayed a good permeation of 43.16% after 210 min.Pomegranate anthocyanins could be used as a safe, stable, homogeneous, nonirritant and effective topical anti-aging drug formulation for aged human people.

read more

PMID: 

Heliyon. 2020 Feb ;6(2):e03330. Epub 2020 Feb 1. PMID: 32025584

Abstract Title: 

Protective effect of royal jelly against diclofenac-induced hepato-renal damage and gastrointestinal ulcerations in rats.

Abstract: 

Objective: Evaluation of traditionally used royal jelly (RJ) for the management of hepato-renal damage and gastrointestinal ulcerations caused by diclofenac.Methods: Forty adult male Wistar rats were allocated into four groups. Rats of the 1group received only saline and served as normal group. The remaining 3 groups received diclofenac (50 mg/kg/day, I.P.) for 7 days. Group 2 served as diclofenac-control group. Groups 3 and 4 received RJ (150 and 300 mg/kg/day, P.O.) respectively for 30 days. Twenty-four hours after the last treatment, blood samples were collected, rats were sacrificed, and livers, kidneys, stomachs&intestines were harvested. Stomachs and intestines were tested for ulcer counts. Serum levels of AST, ALT, creatinine and urea were investigated. Hepatic, renal, gastric and intestinal tissue contents of myeloperoxidase (MPO) and prostaglandin-E2 (PGE2) were measured. Histopathological examinations were also performed followed by immunohistochemical determination of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression.Results: Diclofenac administration caused significant deterioration of all the above mentioned parameters. RJ improved hepatic and renal functions. Gastric and intestinal ulcer counts were significantly ameliorated. Hepatic, renal, gastric and intestinal tissue PGE-2 contents and COX-2 expression were significantly elevated. RJ also significantly reduced MPO content and iNOS expression as compared to diclofenac-control group. Improvements of the histopathological pictures of hepatic, renal, gastric and intestinal tissues were also apparent.Conclusion: The study demonstrates promising protective effects of RJ against diclofenac-induced hepato-renal damage and gastrointestinal ulceration in rats.

read more